This proposed project is for developing the second-generation MR-compatible SPECT system (MRC-SPECT- II). The proposed MRC-SPECT-II system, based on a novel inverted compound-eye (ICE) gamma camera design would offer the potential of dramatically improving SPECT imaging instrumentation from several aspects. First, this approach helps to tackle one of the most limiting aspects of SPECT instrumentation, by offering a dramatically improved sensitivity without sacrificing its resolution capability. The proposed MRC- SPECT-II system could offer an unprecedented sensitivity of 1.5% with a reconstructed imaging resolution of 0.5 mm across and 1.5 cm diameter field-of-view (FOV), and 9% at 1.2 mm spatial resolution (as compared to the typical levels of 0.1% - 0.01% found in modern pre-clinical SPECT instrumentations). This greatly increase in detection sensitivity could potentially provide a radical change in how we might employ SPECT imagining in pre-clinical research by offering a dramatically lowered detection limit and allowing for new imaging procedures that would not be feasible with the current generation of SPECT instrumentations. Second, the ICE-camera design allows the MRC-SPECT-II system to have a significantly reduced physical dimension, while compared to any existing SPECT systems with similar FOV. This would allow the MRC-SPECT-II system (and future MRC-SPECT systems based on similar ICE camera design) to be integrated in most of existing MR scanners. Third, the ICE camera design could also offer dramatically improved sensitivities for scaled-up SPECT scanners for large animals and for human (e.g. brain and heart) imaging applications. Finally, the proposed MRC-SPECT-II system allows for simultaneous SPECT and high-field (9.4T) MR imaging studies. Within this particular project, the MRC-SPECT-II system will be developed and refined for in vivo study of the efficacy and fate of therapeutically engineered neural stem cells in malignant brain tumors, which could help to bring this promising therapeutic approach into clinical practice.